Disulphide bridges

Insulin is built up of two polypeptide chains. A of 21 amino-acids and B of 30 amino-acids, linked by two disulphide bridges. 

M Vasquez. Modeling side-chain conformation. Curr Opm Stiaict Biol 6 217-221, 1996. JM Thornton. Disulphide bridges m globular proteins. J Mol Biol 151 261-287, 1981. 

High thermostabilizing efficiency of polyamine disulphides relative to chemically cross-linked polyethylene is conditioned by the ability to accept macroradicals at the disulphide bridge and imine group. Besides, the presence of paramagnetic centers causes the adherence of macroradicals providing for an extra stabilizing effect [49]. 

AVP and OT are cyclic nonapeptides with a disulphide bridge between the cysteine residues 1 and 6, resulting in a six-amino acid ring and a COOH-terminal a-amidated three-residue tail. OT differs only in two amino acids from AVP lie in position 3, which is essential for OT recqrtor (OTR) stimulation and Leu in position 8. AVP has a Phe in position 3 and an Arg in position 8. Arg 8 is essential for acting upon vasopressin receptors (Fig. 1). Lysipressin, found in pigs and some marsupials, has a Lys in position 8 [1]. 

Vasopressin/Oxytocin. Figure 1 Amino acid sequence of AVP and OT. The disulphide bridge between Cys 1 and Cys 6 is shown. 

A small number of proteins, and again insulin is an example, are synthesized as pro-proteins with an additional amino acid sequence which dictates the final three-dimensional structure. In the case of proinsulin, proteolytic attack cleaves out a stretch of 35 amino acids in the middle of the molecule to generate insulin. The peptide that is removed is known as the C chain. The other chains, A and B, remain crosslinked and thus locked in a stable tertiary stiucture by the disulphide bridges formed when the molecule originally folded as proinsulin. Bacteria have no mechanism for specifically cutting out the folding sequences from pro-hormones and the way of solving this problem is described in a later section. 

Human serum albumin 582 amino acids 17 disulphide bridges Yeast Plasma replacement therapy Normally obtained from plasma but now concern over potential contamination with AIDS virus... 

By far the most studied family of the G-protein-coupled receptors are the rhodopsin-like receptors. These are also the largest group of receptors in number as they include receptors not only for the monoamines, nucleotides, neuropeptides and peptide hormones, but they also include the odorant receptors which number several hundreds of related receptors. These receptors have short N-termini, a conserved disulphide bridge between the TM2-TM3 and TM4—TM5 extracellular domains, and variable-length C-termini. In some cases the C-terminus is myristolyated which by tying the C-terminus to the cell membrane generates a fourth intracellular loop. 

Vasopressin is closely related to oxytocin and both peptides are cyclic in that they contain a disulphide bridge. Although much is known about the peripheral actions of the peptides the extent of our current knowledge of their possible CNS function is that vasopressin appears to act as a cognitive enhancer and has positive effects on learning processes in animals. Vasopressin acts on three receptors, Via and b and a V2 receptor. 

Figure 1. A two-dimensional representation that illustrates the tracing of the interaction lines to give the peak-pass-peak-pass chain representative of the protein backbone, side chains and disulphide bridge. Circles represent passes and squares peaks. 

Figure 2. Correspondence of the calculated backbone trace with that of the reported backbone for BP2 [19], As well, the calculated disulphide bridges are included to illustrate the important role they play in protein structure, binding certain regions together. 

TNF- a was first purified from conditioned medium from HL-60 cells. It has a relative molecular mass of 17 kDa when analysed by SDS-PAGE, but 45 kDa when analysed by gel filtration. Thus, the molecule exists as a non-glycosylated trimer with a pi of 5.3. Each monomer comprises 157 amino acids and contains two cysteine residues that form a disulphide bridge. Trimer formation appears to be due to noncovalent interactions between the monomers. Human TNF-a is synthesised as a 233-amino-acid protein that is proteolytically cleaved during processing. Whilst the 17-kDa form is readily secreted (and hence can function as an extracellular mediator), a 26-kDa transmembrane form has also been identified. This form of TNF-a may thus function in cytotoxicity resulting from cell-cell contact. 

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